NOVEL BROMOPYRROLE ALKALOIDS FROM THE MARINE SPONGE AGELAS OROIDES

Bromopyrrol-derived Alkaloids often found in marine sponges of the genera Agelas, Axinella, Hymeniacidon, Pseudoceratina and Stylotella show a variety of biological activities. In our search for bioactive natural products from marine organisms, a series of bromopyrrole alkaloids have been isolated from the sponge Agelas oroides collected the in Mediterranean Sea. In the preliminary activity tests the Agelas oroides extract exhibited antibacterial activity against a wide array of bacteria, such as the lab strains – E. coli, P. aeruginosa, B. subtilis, S. albus and S. aureus, and marine some environmental strains, as well as, quorum sensing inhibition of the bacterium Chromobacterium violaceum 12472. The crude extract was partitioned successively between petroleum ether, a mixture of 1:1 chloroform/methanol and water. The chloroform/methanol soluble material was separated using different chromatographic methods. Initially, a reversed phase open column chromatography with a gradient of decreasing polarity was applied. The fractions obtained were further separated repeatedly on RP HPLC preparative columns to obtain the pure substances. The structure elucidation of the pure compounds was based on analysis of the spectral data from ¹H-NMR, ¹³C-NMR, COSY, ROESY, HSQC, HMBC and NOE, ESI LC-MS and MS-MS. The study resulted in the isolation and structure elucidation of twelve novel metabolites; agesamide C-G (1-5), dioroidamide A (6), slagenin D (7), bromoagelaspongin A-C (8-10), E-dispacamide (11) and pyrrolosine (12), and 17 known bromopyrrol alkaloids.